Optimal control for mathematical models of cancer therapies. An application of geometric methods (Q2353898): Difference between revisions

The book is a self-contained monograph on the application of tools and techniques of optimal control theory to a wide class of problems arising in oncology. The authors start with a brief introduction to the biomedical background related to cancer development and anticancer therapies, followed by the simplest models of these issues. In the second chapter of the book, the problem of optimal protocols of chemotherapy for homogeneous cancer populations is discussed using compartmental models of the cell cycle. Heterogeneity of tumor cell populations resulting mainly from emergency of drug resistance and its implication for synthesis of optimal protocols is discussed in the third chapter. The authors demonstrate that in this case some parts of the optimal trajectory become singular, which means that the optimal strategy contains composition of maximum tolerated dose protocols (bang-bang control) and continuous maintenance intervals (singular control). The next chapter is devoted to an optimization problem with a quadratic cost functional which, though mathematically interesting, is rather artificial from the biological point of view. The next three chapters are related to the optimization of antiangiogenic therapy and its combination with standard anticancer treatments including chemo- and radiotherapy. The authors formulate optimal control problems for these treatments using a class of population models initiated by \textit{P. Hahnfeldt} et al. [``A dynamical theory of tumor growth, treatment response, and postvascular dormancy'', Cancer Research 59, No. 19, 4770--4775 (1999), \url{http://cancerres.aacrjournals.org/content/59/19/4770}]. The results of a complete synthesis of optimal controlled trajectories show that optimal strategies contain singular controls -- varying administrative schedules of drugs. To make them practically realizable, the authors propose some realistic suboptimal protocols and study their properties. Chapter 8 is devoted to the optimization of chemotherapy taking into account interactions between tumor and the immune system. The authors discuss dynamical properties of the classical \textit{N. V. Stepanova}'s model [``Course of the immune reaction during the development of a malignant tumour'', Biophysics 24, 917--923 (1980)] and optimize the combination of chemotherapy with immunotherapy (in the form of an immune boost). Moreover, they consider a combination of Stepanova's and Halnfeldt's models to discuss the effect of antitumor, antiangiogenic and immune stimulatory effects. The book contains two appendixes. The first one presents a review of the main results in optimal control with emphasis on geometric methods. The second one contains mathematical proofs of theorems presented in the book. The book is in large part a critical survey of the authors' work, but they give also credit to other researchers. All considerations are presented in a rigorous mathematical language, but the authors do their best to be understandable also for researchers involved in systems biology with a moderate mathematical background.